The objective of this proposal is to determine the mechanism by which butylated hydroxyanisole (BHA) and related compounds can inhibit carcinogenesis by the environmental N-nitrosamines, N-nitrosodimethylamine (DMN), N-nitrosodiethylamine (DEN), N-nitrosopurrolidine (NPYR), N-nitrosopiperidine (NPIP), and N-nitrosomorpholine (NMOR). The effects of BHA on levels of electrophiles available to react with DNA of target organs will be determined. Specifically, the levels of DNA alkylation by DMN and DEN in mouse lung and rat liver of BHA-treated and control animals will be determined. The levels of available electrophiles generated by a-hydroxylation of NPYR, NPIP and NMOR will also be determined in organ cultures of target tissues from BHA-treated and control animals. In cases where BHA pretreatment results in a decrease in available electrophiles, the role of changes in microsomal metabolism or of increased levels of tissue gluathione will be investigated. The effects of structure on potential inhibitor activity will also be investigated for a series of compounds structurally analagous to BHA. To correlate metabolic changes with chemopreventive activity, bioassays of the nitrosamines in BHA-treated and control mice, rats, and hamsters will be performed. These studies are designed to form the basis for a practical approach to chemoprevention of cancer caused by low level exposures to nitrosamines.